High levels of thyrotropin-releasing hormone receptors activate programmed cell death in human pancreatic precursors.
OBJECTIVE
Thyrotropin-releasing hormone (TRH) is expressed in rodent and human adult pancreata and in mouse pancreas during embryonic development. However, expression of TRH receptors (TRHRs) in the pancreas is controversial. We sought to provide evidence that the TRH/TRHR system might play a role in fetal development.


METHODS
We used quantitative reverse transcription-polymerase chain reaction to measure TRH and TRHR messenger RNA (mRNA). To study the effects of TRHR expression in a pancreatic progenitor population, we expressed TRHRs in human islet-derived precursor cells (hIPCs) by infection with adenoviral vector AdCMVmTRHR. Thyrotropin-releasing hormone receptor signaling was measured as inositol phosphate production and intracellular calcium transients. Thyrotropin-releasing hormone receptor expression was measured by [H]methyl-TRH binding. Apoptosis was monitored by release of cytochrome c from mitochondria.


RESULTS
We show that TRH mRNA is expressed in human fetal and adult pancreata, and that TRHR mRNA is expressed in fetal human pancreas but not in adult human pancreas. Thyrotropin-releasing hormone receptors expressed in hIPCs were shown to signal normally. Most importantly, TRH treatment for several days stimulated apoptosis in hIPCs expressing approximately 400,000 TRHRs per cell.


CONCLUSIONS
These findings suggest a possible role for TRH/TRHR signaling in pancreatic precursors to promote programmed cell death, a normal constituent of morphogenesis during embryonic development in humans.
Mulla
Christopher M
CM
Clinical Endocrinology Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-8029, USA.
Geras-Raaka
Elizabeth
E
Raaka
Bruce M
BM
Gershengorn
Marvin C
MC
D017209:Apoptosis; D006801:Humans; D010179:Pancreas / Q000166:cytology* / Q000196:embryology*; D012333:RNA, Messenger / Q000032:analysis; D018025:Receptors, Thyrotropin-Releasing Hormone / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D013973:Thyrotropin-Releasing Hormone / Q000235:genetics
D012333:RNA, Messenger; D018025:Receptors, Thyrotropin-Releasing Hormone; D013973:Thyrotropin-Releasing Hormone